BIOPHARMACEUTICAL MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 352

FMEA analysis or other risk assessment methodologies are an effective way of
identifying and mitigating these common risks at all stages. Designed experiments
may also be used to identify critical parameters, their interactions, and their
impact on process limits. Given this information, analysts can validate the process
to establish reproducibility within identified ranges and demonstrate the adequacy
of control strategies for identified risks.
In addition to the manufacturing process, primary packaging is critical as
a biotechnology product may be sensitive to a variety of environmental fac-
tors such as surface of its primary package, temperature, moisture, and light.
Primary packaging must also be characterized for extractables and leachables
to ensure absence of adverse interactions between these components and the
product.
Finally, the product is packaged and ready to begin its journey to a patient.
Distribution processes must be carefully qualified and controlled to preclude
adverse product interactions. Typical distribution tests address product impact
by emulating transportation challenges such as vibration, time, dropping, etc.
Through such testing, adequate secondary and tertiary packaging may be designed
and distribution processes developed so that product quality is not compromised.
The use of risk management to identify, assess, and mitigate risks associated
with biopharmaceutical manufacturing can reduce the impact of unplanned and
uncontrolled events that periodically occur. Risk management activities result in
more robust processes that are capable of handling a broader range of inputs
while still yielding a product of consistent quality. Although risk assessments
require somewhat more effort (time and resource) to complete, they ultimately
benefit both the manufacturer and the final patient.
APPENDIX A: APPLICATION OF RISK MANAGEMENT TOOLS
TO BIOPHARMACEUTICAL MANUFACTURING
A.1 Case Study: Raw Material Hazard Analysis
This example addresses the use of a hazard analysis to identify the potential
hazards associated with the use of fetal bovine serum (FBS) to manufacture a
master cell bank for a biological product. The example follows the general outline
provided in PDA TR44 and utilizes the same scales [33].
A.2 Prerequisites
Initiation : Risk assessments should begin with careful planning to establish the
scope and boundaries of the task at hand. A basic risk question that addresses the
issues to be considered should be identified. For example, one might ask “what
are the risks associated with the use of FBS obtained from ABC country for the
production of a master cell bank for XYZ product line?”
A tool used to map the process at a high level and establish boundaries around
the analysis is the SIPOC analysis. The acronym SIPOC stands for supplier,